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Enhanced clearing of Candida biofilms on a 3D urothelial cell in vitro model using lysozyme-functionalized fluconazole-loaded shellac nanoparticles

Wang, Anheng; Weldrick, Paul J.; Madden, Leigh A.; Paunov, Vesselin N.


Anheng Wang

Paul J. Weldrick

Vesselin N. Paunov


Candida urinary tract biofilms are increasingly witnessed in nosocomial infections due to reduced immunity of patients and the hospital ecosystem. The indwelling devices utilized to support patients with urethral diseases that connect the unsterilized external environment with the internal environment of the patient are another significant source of urinary tract biofilm infections. Recently, nanoparticle (NP)-associated therapeutics have gained traction in a number of areas, including fighting antibiotic-resistant bacterial biofilm infection. However, most studies on nanotherapeutic delivery have only been carried out in laboratory settings rather than in clinical trials due to the lack of precise in vitro and in vivo models for testing their efficiency. Here we develop a novel biofilm-infected 3D human urothelial cell culture model to test the efficiency of nanoparticle (NP)-based antifungal therapeutics. The NPs were designed based on shellac cores, loaded with fluconazole and coated with the cationic enzyme lysozyme. Our formulation of 0.2 wt% lysozyme-coated 0.02 wt% fluconazole-loaded 0.2 wt% shellac NPs, sterically stabilised by 0.25 wt% poloxamer 407, showed an enhanced efficiency in removing Candida albicans biofilms formed on 3D layer of urothelial cell clusteroids. The NP formulation exhibited low toxicity to urothelial cells. This study provides a reliable in vitro model for Candida urinary tract biofilm infections, which could potentially replace animal models in the testing of such antifungal nanotechnologies. The reproducibility and availability of a well-defined biofilm-infected 3D urothelial cell culture model give valuable insights into the formation and clearing of fungal biofilms and could accelerate the clinical use of antifungal nanotherapeutics.


Wang, A., Weldrick, P. J., Madden, L. A., & Paunov, V. N. (2021). Enhanced clearing of Candida biofilms on a 3D urothelial cell in vitro model using lysozyme-functionalized fluconazole-loaded shellac nanoparticles. Biomaterials science / Royal Society of Chemistry, 9(20), 6927-6939.

Journal Article Type Article
Acceptance Date Aug 28, 2021
Online Publication Date Sep 16, 2021
Publication Date Oct 21, 2021
Deposit Date Sep 16, 2021
Publicly Available Date Oct 27, 2022
Journal Biomaterials Science
Print ISSN 2047-4830
Electronic ISSN 2047-4849
Publisher Royal Society of Chemistry
Peer Reviewed Peer Reviewed
Volume 9
Issue 20
Pages 6927-6939
Keywords General Materials Science; Biomedical Engineering
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Copyright Statement
© The Royal Society of Chemistry 2021

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